Table 1.

The clinical manifestations of radiation injury, the prevalence of late, fibrosis-related radiation injuries, and frequently associated cancers.

Site of fibrosis	Clinical features	Prevalence of late, fibrosis-related radiation injuriesa	Frequently associated cancer types	References
Skin	Oedema, Alopecia, Dermatitis, Dermal Contraction, Dermal Thickening, Impaired Wound Healing, Ulceration	•Up to 30% of patients receiving RT to the breast or chest wall may develop severe fibrosis.	Breast, HNC, Sarcomas, Skin	22,23
Lungs	Coughing, Dyspnoea, Chest Pain, Impaired O2 Delivery, Interstitial Oedema	•Average incidence of 16–28% of radiation-induced lung fibrosis after radiotherapy. •∼5–50% of patients receiving thoracic RT may develop radiation-induced lung fibrosis. •Up to 35% of patients receiving RT for lung or breast cancer develop radiation pneumonitis and are at high risk of developing fibrosis.	Lymphoma, Breast, Lung, Mesothelioma, Oesophageal, Thymic	13,24, 25, 26
Heart/vasculature	Angina, Radiation-Induced Heart Disease, Vessel Stenosis, Valvular Disease, Myocardial Infarction, Stroke, Right/Left Ventricular Dysfunction, Conduction Abnormalities, Arrhythmias, Pericardial Disease	•∼9% of breast cancer survivors develop left ventricular dysfunction. •∼25% of patients receiving significant mediastinal RT develop cardiomyopathy, and ∼70–90% show image-based evidence of pericardial disease. •Up to 4–5% of cancer patients treated with RT will develop conduction system pathologies. •Prevalence of valvulopathy is up to 26% at 10 years and up to 60% at 20 years post-RT.	Breast, Lymphoma, Lung	27, 28, 29, 30, 31
Musculature	Muscle Weakness/Atrophy, Limited Range of Motion, Asymmetric Neuropathies	•Up to 45% of HNC patients receiving curative doses of RT develop trismus. •∼22% of HNC patients receiving RT develop brachial plexopathies.	General Consequence of Muscle Irradiation and/or Peripheral Nerve Damage	27,32, 33, 34
Nervous system	Neuropathic Pain, Sensory Loss, Impaired Muscle Control, Weakness		HNC, HL, Nasopharyngeal, Direct Radiation-Induced Damage
Gastrointestinal tract (oesophagus, small and large bowel, liver)	Dysphagia, Nausea, Abdominal Pain, Dysmotility, Constipation, Diarrhoea, Strictures, Fistulas, Proctitis, Faecal Incontinence	•∼5–10% of patients receiving RT for pelvic or abdominal cancers develop severe bowel toxicity, including lumen narrowing and transmural fibrosis. •∼10–15% of cervix cancer survivors develop severe bowel toxicity post-RT. •∼6–66% of patients receiving 30–35 Gy of hepatic radiation may develop significant radiation-induced liver disease.	GI (Stomach, Small and Large Bowel, Rectal, Anal, Liver), GU (Prostate, Bladder), Gynaecologic (Cervical, Uterine)	27,35, 36, 37
Genitourinary tract	Haematuria, Cystitis, Urinary Incontinence, Reproductive Dysfunction, Urinary Strictures, Fistulae, Strictures	•∼8–12% of cervix cancer patients receiving RT develop urinary sequelae. •∼4–11% of prostate cancer survivors develop radiation cystitis.	GI, GU, Gynaecologic	27,38,39
Gynaecologic	Vaginal Narrowing/Shortening, Pain, Dryness, Vaginal Stenosis (VS), Ulceration, Necrosis, Atrophy	•∼38% of Stage IB to Stage IV cervix cancer patients treated with pelvic and/or vaginal RT or brachytherapy develop VS. •∼16–43% of patients with locally advanced cervix cancer may develop VS from brachytherapy, increasing with RT dose.	Cervical, Vaginal	40,41

^aPrevalence of fibrosis-related radiation injuries may potentially be related to fibrosis prevalence, but there is no clear demarcation between late radiation toxicity and radiation fibrosis statistics in most studies.